• The serine/threonine kinase mTOR is a downstream effector of the PI3K/AKT pathway, and forms two distinct multiprotein complexes, mTORC1 and mTORC2. (wikipedia.org)
  • Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
  • The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. (bvsalud.org)
  • Moreover, AKT signaling contributes to oncogenesis through activating multiple downstream effector molecules. (biomedcentral.com)
  • The mGluR5-ERK1/2 pathway is not constitutively overactive in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to basal ERK1/2 activation in the absence of FMRP. (jneurosci.org)
  • We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. (jneurosci.org)
  • These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS. (jneurosci.org)
  • high bacteria are as proteins of pathway ATM rise, either as acids for greenhouse initiation or for the dehydrogenase of binding eIF2 disorders. (evakoch.com)
  • The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. (biomedcentral.com)
  • Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2 -dependent manner. (biomedcentral.com)
  • IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR. (biomedcentral.com)
  • Phosphatidylinositol-3-kinase (PI3-K) pathway has been reported as an important intracellular mediator frequently activated in cancer cells [ 2 ]. (biomedcentral.com)
  • This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. (babraham.ac.uk)
  • ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled? (babraham.ac.uk)
  • The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (babraham.ac.uk)
  • Homeotic mutations in Drosophila can result in dramatic phenotypes that suggest the possibility for rapid morphological evolution, but dissection of the genetic pathway downstream of Ultrabithorax is beginning to reveal how wing morphology may have evolved by more gradual transformations. (lookformedical.com)
  • In order to identify the target molecule of miRNA-1908, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human glioblastoma tissues. (biomedcentral.com)
  • miRNA-1908 functions as an oncogene in glioblastoma by repressing the PTEN pathway. (biomedcentral.com)
  • To figure out regardless of whether ERK1/2 signaling pathway mediates the motion of taurine on cell proliferation, P5 hippocampal stem/ progenitor cells have been uncovered to the ERK1/two inhibitor PD98059 (ten mM) followed by taurine therapy. (adenosine-receptor.com)
  • The mTORC1 signaling cascade is activated by phosphorylated AKT and results in phosphorylation of S6K1, and 4EBP1, which lead to mRNA translation. (wikipedia.org)
  • Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile X mental retardation protein), a repressor of mRNA translation. (jneurosci.org)
  • Our data suggest that elevated protein synthesis in the Fmr1 KO is due to saturation of mRNA translation downstream of the MAP kinase ERK1/2 which is basally activated by mGluR5. (jneurosci.org)
  • Recombinant HIPKs and DYRK1A are auto-activated and phosphorylate the negative elongation factor SPT5, the transcription factor c-Myc, and the C-terminal domain of RNA polymerase II, suggesting a direct function in transcriptional regulation. (nature.com)
  • DYRKs are named after their characteristic dual-specificity, as they auto-phosphorylate a conserved tyrosine in their activation loop, but phosphorylate substrates on serine and threonine residues 2 . (nature.com)
  • In most metazoans, GCN2 is one of the four known kinases that phosphorylate eukaryotic initiation factor 2, α subunit (eIF2α) to inhibit translation initiation [ 19 ]. (biomedcentral.com)
  • This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
  • This may be relevant to the suggestion of kinase-independent effects of ERK1/2 and the therapeutic use of ERKi. (babraham.ac.uk)
  • Levels of proteins, including Cyt C, Bcl-2/BAX, and Nrf2 /HO-1-associated proteins, were determined by western blotting and immunofluorescence. (sdbonline.org)
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
  • Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. (lookformedical.com)
  • Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. (lookformedical.com)
  • These are frequently activated by fusion to other transcriptional proteins resulting in chimeric transcription factors. (stanford.edu)
  • They studied 128 proteins, called trans-acting factors , which are known to regulate gene expression by binding to regulatory regions within the genome. (pharmaceuticalintelligence.com)
  • In addition, there are non-cellular components such as growth factors, cytokines, and extracellular matrix that surround the tumor cells. (biomedcentral.com)
  • They are responsible for the regulation of various pro- and anti-tumor factors and play a role in the progression of the disease. (biomedcentral.com)
  • In accordance, the aberrant expression of RBX2 will lead to dysregulation of many signaling pathways, which is crucial for tumor initiation and growth. (bvsalud.org)
  • Due to the unobvious early symptoms and the influence of some adverse factors such as tumor heterogeneity and low immunogenicity, patients with advanced gastric cancer (AGC) cannot benefit significantly from treatments such as radical surgical resection, radiotherapy, chemotherapy, and targeted therapy. (frontiersin.org)
  • Several downstream pathways that regulate cell-cycle progression, translation, initiation, transcriptional stress responses, protein stability, and survival of cells are signaling through mTOR. (wikipedia.org)
  • DR acts by promoting stress response pathways and preventing age-related functional decline, delaying the appearance of cardiovascular diseases, type 2 diabetes, and neurodegeneration in mammals, including non-human primates [ 6 ]. (biomedcentral.com)
  • According to the metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein synthesis downstream of mGluR5 activation causes the synaptic pathophysiology that underlies multiple aspects of FXS. (jneurosci.org)
  • We find that elevated basal protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian target of rapamycin). (jneurosci.org)
  • Evolutionarily conserved, these 17-22 nucleotide long molecules regulate gene expression at post-transcriptional level generally by repressing translation or increasing degradation of messenger RNAs (mRNAs). (biomedcentral.com)
  • The FAT domain consists of repeats, referred to as HEAT (Huntingtin, Elongation factor 3, A subunit of protein phosphatase 2A and TOR1). (wikipedia.org)
  • Here, using a CRISPRi screen targeting chromatin factors, we identified the nucleosome-remodeling factor (NURF) subunit BPTF as an essential regulator of AML cell survival. (x-mol.com)
  • ERK1/2 inhibitors act as monovalent degraders inducing ubiquitylation and proteasome-dependent turnover of ERK2, but not ERK1. (babraham.ac.uk)
  • Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)
  • These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)
  • Furthermore, inhibitors to ERK1/2 (ERK1/2i) have also been developed to counteract ERK1/2 signalling. (babraham.ac.uk)
  • Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. (biomedcentral.com)
  • Nrf2 is a master eukaryotic redox-active factor and belongs to Cap 'n' Collar (Cnc)-bZIP (basic leucine zipper) family of transcription factors. (springer.com)
  • Genes that encode highly conserved TRANSCRIPTION FACTORS that control positional identity of cells (BODY PATTERNING) and MORPHOGENESIS throughout development. (lookformedical.com)
  • 2023 ). By modulating these processes, m 6 A modifications have a profound impact on the fate and cellular functions of the modified RNA molecules, influencing RNA splicing, export, translation, and stability. (biomedcentral.com)
  • By testing multiple isogenic bacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis. (iasp-pain.org)
  • Finally, the C-terminus of HIPK1-3 comprises a region rich in serine, glutamine, and alanine (SQA) residues, which is involved in the interaction with different co-factors 14 . (nature.com)
  • however, mRNAs encoding a subset of factors important for error-free replication and chromosome segregation, including TIPIN, PLK2 and PLK3, remain at low abundance. (babraham.ac.uk)
  • RBX2 (RING box protein 2), also known as ROC2 (Regulator of Cullins 2), RNF7 (RING Finger Protein 7), or SAG (Sensitive to Apoptosis Gene) is a key component of the Cullin-RING-type E3 ubiquitin ligases (CRLs) and overexpressed in various human cancers. (bvsalud.org)
  • DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4-RING E3 ubiquitin ligase (CRL4) complexes. (bvsalud.org)
  • The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)
  • Collectively, this study provides the first evidence that transient levels of the evolutionarily conserved factor RACK1 are critical for adult SC activation and proper skeletal muscle regeneration, favoring the efficient progression of SC from a committed to a fully differentiated state. (sdbonline.org)
  • Additionally, the TME is influenced by m 6 A regulatory factors, impacting the progression and prognosis of CRC. (biomedcentral.com)
  • encoded by Nfe2l2 gene) is a transcription factor responsible for the regulation of cellular redox balance and protective antioxidant and phase II detoxification responses in mammals [ 1 , 2 ]. (springer.com)
  • This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors. (springer.com)
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
  • The Bcl-2 homology 3 (BH3) domain is crucial for the death-inducing and dimerization properties of pro-apoptotic members of the Bcl-2 protein family, including Bak, Bax, and Bad. (lookformedical.com)
  • Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
  • This latter finding is likely to preclude the existence of cryptic transcription factor binding site(s) in the 5'-untranslated region of p27 gene. (biomedcentral.com)
  • This leads to translation of an alternative and functional open reading frame of the ATF4 gene ( atf-5 in C. elegans ) [ 20 , 21 ]. (biomedcentral.com)
  • Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism. (lookformedical.com)
  • 2) We have discovered a group of oncoproteins that are implicated in long-term maintenance of gene expression through their effects on the state of chromatin. (stanford.edu)
  • neighboring Expression represses to underlie identified by the oxidoreductase of Rev with importin-beta and B23 and signaling at the Syndecan transcription through proteases between acts and hours. (evakoch.com)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • Being an integral part of the eukaryotic transcriptome, miRNAs are regarded as vital regulators of diverse developmental and physiological processes. (eurekaselect.com)
  • Here, we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity. (bvsalud.org)
  • Single cells and organisms may adapt to harmful oxidative stress conditions, through stress-activated factors. (springer.com)
  • ChIP-QPCR analysis revealed that ATF4, an ER-stress inducible transcription factor, directly activated Zbtb38 transcription by binding to the Zbtb38 promoter. (oncotarget.com)
  • Thus, we identify a mechanism of action for a pruritogenic bacterial factor and demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch. (iasp-pain.org)
  • Distinct and overlapping factors are involved in lifespan extension by bacterial DR (bDR) and liquid DR (lDR) - two protocols of bacterial dilution in liquid cultures. (biomedcentral.com)
  • The researchers used 238 data sets generated by the ENCODE project to study the specific DNA sequences bound by each of the 128 trans-acting factors. (pharmaceuticalintelligence.com)
  • It is also possible to analyze the underlying factors that contribute to behavior in C. elegans , because it has a relatively simple and well-defined nervous system. (elifesciences.org)
  • Xie, Boyle and Snyder designed a machine-learning algorithm to analyze all the data and identify which trans-acting factors tend to be seen together and which DNA sequences they prefer. (pharmaceuticalintelligence.com)
  • rather adaptations in MOR function may be determined by multiple factors such as subcellular receptor distribution, influence of local circuitry and sex. (iasp-pain.org)
  • The genetic model of DR - the eat-2 mutant - has a decreased pumping rate, thus ingesting less bacteria, and requires the FoxA transcription factor PHA-4 [ 8 ] and the dimethoxy ubiquinone hydroxylase CLK-1 [ 9 ] to extend its lifespan. (biomedcentral.com)
  • We determined a 2.76 -resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. (regenerativemedicine.net)
  • These lipid modifications are mainly palmitoylation or prenylations, being farnesylation and geranyl-geranylation the most frequent post-translation modifications [ 4 ]. (biomedcentral.com)
  • Two factors concur to determine specific Rho GTPase function: tissue specificity of GTPase effectors and distinct intracellular localizations of closely related Rho GTPases, due to different lipid modifications [ 1 ]. (biomedcentral.com)
  • Finally, cells have been washed and resuspended in tradition media supplemented with FGF-2 (R&D Techniques) and EGF (Merck), equally at 20 ng/ml in five mg/ml heparin. (adenosine-receptor.com)
  • mTORC2 is activated by growth factors, phosphorylates PKCα, AKT and paxillin, and regulates the activity of the small GTPase, Rac, and Rho related to cell survival, migration and regulation of the actin cytoskeleton. (wikipedia.org)
  • Fostering discussion and collaboration that speeds up the acquisition of new knowledge and its translation into novel pain treatments. (iasp-pain.org)